Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer

The Prostate ◽  
2015 ◽  
Vol 75 (14) ◽  
pp. 1586-1600 ◽  
Author(s):  
Katarina Davalieva ◽  
Ivana Maleva Kostovska ◽  
Sanja Kiprijanovska ◽  
Katerina Markoska ◽  
Katerina Kubelka-Sabit ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Tissue ◽  
Proteomics Analysis ◽  
2D Dige ◽  
Benign Prostate

scholarly journals Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 537 ◽  
Author(s):  
Renuka Sriram ◽  
Mark Van Criekinge ◽  
Justin DeLos Santos ◽  
Fayyaz Ahamed ◽  
Hecong Qin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Magnetic Resonance ◽  
Gleason Score ◽  
Prostate Tissue ◽  
Resonance Spectroscopy ◽  
Low Grade ◽  
High Grade ◽  
Metabolic Alterations ◽  
Ldh Activity ◽  
Benign Prostate

Non-invasive assessment of the biological aggressiveness of prostate cancer (PCa) is needed for men with localized disease. Hyperpolarized (HP) 13C magnetic resonance (MR) spectroscopy is a powerful approach to image metabolism, specifically the conversion of HP [1-13C]pyruvate to [1-13C]lactate, catalyzed by lactate dehydrogenase (LDH). Significant increase in tumor lactate was measured in high-grade PCa relative to benign and low-grade cancer, suggesting that HP 13C MR could distinguish low-risk (Gleason score ≤3 + 4) from high-risk (Gleason score ≥4 + 3) PCa. To test this and the ability of HP 13C MR to detect these metabolic changes, we cultured prostate tissues in an MR-compatible bioreactor under continuous perfusion. 31P spectra demonstrated good viability and dynamic HP 13C-pyruvate MR demonstrated that high-grade PCa had significantly increased lactate efflux compared to low-grade PCa and benign prostate tissue. These metabolic differences are attributed to significantly increased LDHA expression and LDH activity, as well as significantly increased monocarboxylate transporter 4 (MCT4) expression in high- versus low- grade PCa. Moreover, lactate efflux, LDH activity, and MCT4 expression were not different between low-grade PCa and benign prostate tissues, indicating that these metabolic alterations are specific for high-grade disease. These distinctive metabolic alterations can be used to differentiate high-grade PCa from low-grade PCa and benign prostate tissues using clinically translatable HP [1-13C]pyruvate MR.

scholarly journals Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer

2018 ◽  
Vol 25 (9) ◽  
pp. 807-819 ◽  
Author(s):  
Matias Knuuttila ◽  
Arfa Mehmood ◽  
Jenni Mäki-Jouppila ◽  
Henrik Ryberg ◽  
Pekka Taimen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Alternative Pathway ◽  
Prostate Tissue ◽  
Cancer Therapies ◽  
Serum Samples ◽  
Androgen Metabolism ◽  
Tissue Specimens ◽  
Regulated Gene Expression ◽  
Benign Prostate

Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG-negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG-positive tumors. TMPRSS2-ERG-positive and -negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors. Thus, patients with TMPRSS2-ERG-positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.

Increased cholesterol synthesis via squalene monooxygenase to predict lethal prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 77-77 ◽  
Author(s):  
Konrad Hermann Stopsack ◽  
Travis Gerke ◽  
James Robert Cerhan ◽  
Lorelei A. Mucci ◽  
Jennifer R. Rider
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cholesterol Synthesis ◽  
Watchful Waiting ◽  
Prostate Tissue ◽  
Health Study ◽  
Squalene Monooxygenase ◽  
Increased Risk ◽  
The Mean ◽  
Benign Prostate

77 Background: Prostate cancer cells rely on cholesterol for proliferation and androgen production. We recently demonstrated that increased expression of the second key enzyme of cholesterol synthesis, squalene monooxygenase (SQLE), is associated with higher prostate cancer-specific mortality (PCSM). We here validate findings in two additional prospective studies and investigate putative mechanisms. Methods: We analyzed the prospective prostatectomy cohorts within the Health Professionals Follow-up Study (HPFS) and the Physicians’ Health Study (PHS) as well as initially expectantly managed patients in the Swedish Watchful Waiting Study (SWWS). 258 lethal cancer cases and 469 patients who survived > 8 years without metastases were included. SQLE mRNA was measured in tumor specimens at diagnosis of all patients and in benign prostate tissue of 197 patients. Markers of tumor angiogenesis were assessed via immunohistochemistry in 169 HPFS patients. We estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Results: Higher SQLE expression was confirmed to be predictive of higher PCSM in the validation prostatectomy cohort PHS. Combining the two prostatectomy cohorts, men with high SQLE expression ( > 1 standard deviation above the mean) were 6.7 times (95% CI, 2.9 to 15.8; p < 0.001) more likely to die from their cancer compared to men with the mean level of SQLE expression. A 10% higher ratio of SQLE mRNA expression in tumor vs. benign prostate tissue of the same patient was predictive of 42% higher PCSM (95% CI, 15% to 74%). Higher SQLE expression was strongly associated with increased angiogenesis markers (all p ≤ 0.001). This increased risk associated with high SQLE expression was not modified by statin use (p ≥ 0.52). In initially untreated patients in SWWS, a more modest association of tumor SQLE expression with PCSM was observed (p = 0.047). Conclusions: SQLE, the second rate-limiting enzyme of cholesterol synthesis, is associated with prostate cancer progression. Its expression at cancer diagnosis is predictive of lethal disease both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

UP-1.125: Importance of miRNAs Expression in Prostate Cancer and Benign Prostate Tissue

Urology ◽  
2009 ◽  
Vol 74 (4) ◽  
pp. S209
Author(s):  
J. Klecka ◽  
M. Pesta ◽  
M. Hora ◽  
V. Kulda ◽  
L. Holubec ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Tissue ◽  
Mirnas Expression ◽  
Benign Prostate

scholarly journals Use of Aspirin and Statins in Relation to Inflammation in Benign Prostate Tissue in the Placebo Arm of the Prostate Cancer Prevention Trial

2020 ◽  
Vol 13 (10) ◽  
pp. 853-862
Author(s):  
Lauren M. Hurwitz ◽  
Ibrahim Kulac ◽  
Berrak Gumuskaya ◽  
Javier A. Baena Del Valle ◽  
Ines Benedetti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Prevention ◽  
Prevention Trial ◽  
Prostate Tissue ◽  
Prostate Cancer Prevention ◽  
Prostate Cancer Prevention Trial ◽  
Benign Prostate

scholarly journals Identification and Validation of Potential New Biomarkers for Prostate Cancer Diagnosis and Prognosis Using 2D-DIGE and MS

2015 ◽  
Vol 2015 ◽  
pp. 1-23 ◽  
Author(s):  
Cordelia Geisler ◽  
Nadine T. Gaisa ◽  
David Pfister ◽  
Susanne Fuessel ◽  
Glen Kristiansen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Western Blot ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Prostate Tissue ◽  
Biochemical Relapse ◽  
Prostate Cancer Diagnosis ◽  
2D Dige ◽  
Diagnosis And Prognosis ◽  
New Biomarkers

This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P< 0.044) in prostate cancer, while vinculin showed significant upregulation (P< 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P= 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P= 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P= 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique.

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